Kristan Steffen
Mentor: Brian KennedyBox: 357350
Phone: 206-616-9484
Email: stef0124@u.washington.edu
Kristan Steffen is a graduate student studying yeast aging in Brian Kennedy's lab. The budding yeast Saccharomyces cerevisiae undergo a finite number of replicative cycles before death. This number, the number of daughter cells produced by a single mother cell, is defined as its replicative lifespan. Ms. Steffen's work focuses on understanding the complex genetic pathways that regulate yeast replicative lifespan.
Using a genome-wide approach to identify novel aging pathways in yeast, the Kennedy lab identified the highly conserved Tor (target of rapamycin) signaling pathway as a major regulator of replicative aging. Reduced signaling through this pathway increases lifespan in yeast, as well as many other model organisms, including C. elegans and D. melanogaster. In response to nutrients, the Tor signaling pathway regulates multiple downstream processes, including autophagy, stress response, protein turnover, cell growth, and ribosome biogenesis. A major focus of Ms. Steffen's work has been to identify which of these downstream processes are most important for lifespan regulation.
Recent evidence indicates that the 60S ribosomal subunit is a major regulator of lifespan.
Reduction of 60S subunit is sufficient to increase replicative lifespan by up to 50%. One mechanism by which reduced 60S subunit levels leads to lifespan extension is through induction of Gcn4, a highly-conserved nutrient-responsive transcription factor. Gcn4 expression is translationally-regulated such that its synthesis is increased during nutritional stress. Consistently, dietary restricted cells, or cells lacking TOR1 or SCH9, each require Gcn4 for full lifespan extension. These data warrant further investigation of translationally-regulated control of lifespan, and indicate that this may be a conserved mechanism by which lifespan is regulated.
Publications
Steffen KK, MacKay VL, Kerr EO, Tsuchiya M, Hu D, Fox LA, Dang N, Johnston ED, Oakes JA, Tchao BN, Pak DN, Fields S, Kennedy BK, Kaeberlein M. Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell. 2008 Apr 18;133(2):292-302.
Kennedy BK, Steffen KK, Kaeberlein M. Ruminations on dietary restriction and aging.
Cell Mol Life Sci. 2007 Jun;64(11):1323-8. Review.
Tsuchiya M, Dang N, Kerr EO, Hu D, Steffen KK, Oakes JA, Kennedy BK, Kaeberlein M.
Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast.
Aging Cell. 2006 Dec;5(6):505-14.
Kaeberlein M, Steffen KK, Hu D, Dang N, Kerr EO, Tsuchiya M, Fields S, Kennedy BK.
Comment on "HST2 mediates SIR2-independent life-span extension by calorie restriction".
Science. 2006 Jun 2;312(5778):1312; author reply 1312.
Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005 Nov 18;310(5751):1193-6.